1. Field of the Invention
The present invention relates to a process for producing an optically active 4-hydroxy-2-ketoglutaric acid in which a biocatalyst having an activity for formation of the optically active 4-hydroxy-2-ketoglutaric acid from pyruvic acid and glyoxylic acid is used to produce the optically active 4-hydroxy-2-ketoglutaric acid from pyruvic acid or a compound capable of being converted into pyruvic acid, and glyoxylic acid. The optically active 4-hydroxy-2-ketoglutaric acid is useful as a starting material for synthesizing a medicament.
2. Description of the Prior Art
As conventional methods for producing the optically active 4-hydroxy-2-ketoglutaric acid, chemical deamination of threo- and erythro-4-hydroxy-L-glutamic acid to obtain L- and D-4-hydroxy-2-ketoglutaric acid, respectively (J. Biol. Chem., 288, 3660 (1963)) and resolution of DL-4-hydroxy-2-ketoglutaric acid synthesized from oxaloacetic acid and glyoxylic acid into D- and L-form (Methods in Enzymology, 17 part B, 253) are known. It is also possible to enzymatically synthesize 4-hydroxy-2-ketoglutaric acid from pyruvic acid and glyoxylic acid by using ketohydroxyglutaric acid aldolase present in animals and E. coli. However, the 4-hydroxy-2-ketoglutaric acids obtained by these methods are known to be only mixtures of D- and L-forms (Methods in Enzymology, 41 part B, 115).
These conventional methods are insufficient for the industrial application due to the following points: (1) the starting materials are expensive; (2) resolution step of DL-form is required; (3) yield is low, etc. Consequently, there exists a need for development of a method for producing the optically active 4-hydroxy-2-ketoglutaric acid which is industrially applicable and advantageous.